New insights into the mechanisms and therapeutic strategies of chondrocyte autophagy in osteoarthritis.

IF 4.8 3区 医学 Q1 GENETICS & HEREDITY
Journal of Molecular Medicine-Jmm Pub Date : 2024-10-01 Epub Date: 2024-08-15 DOI:10.1007/s00109-024-02473-1
Lujia Tang, Jiatong Ding, Kangping Yang, Zhen Zong, Rui Wu, Hui Li
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引用次数: 0

Abstract

Osteoarthritis (OA) is a chronic joint disease with an unclear cause characterized by secondary osteophytes and degenerative changes in the articular cartilage. More than 250 million people are expected to be affected by it by 2050, putting a tremendous socioeconomic strain on the entire world. OA cannot currently be treated with any effective medications that change the illness. Over time, chondrocytes undergo gradual metabolic, structural, and functional changes as a result of aging or abuse. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte homeostasis. By continuously recycling and rebuilding macromolecules or organelles, autophagy functions as a crucial regulatory system to maintain homeostasis during an individual's growth and development. This review uses chondrocytes as its starting point and establishes a strong connection between autophagy and osteoarthritis in order to thoroughly examine the mechanisms behind chondrocyte autophagy in osteoarthritis. Biomarkers of chondrocyte autophagy will be identified, and prospective targeted medications and novel treatment approaches for slowing or preventing the course of OA will be developed based on chondrocyte senescence, autophagy, and apoptosis in OA. KEY MESSAGES: Currently, OA has not been treated with any drugs that can effectively cure it. We hope that by exploring specific targets in the course of osteoarthritis, we can promote the progress of treatment strategies. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte balance. Through the continuous recovery and reconstruction of macromolecules or organelles, autophagy is an important regulatory system for maintaining homeostasis during individual growth and development. In this paper, the close relationship between autophagy and osteoarthritis was established with chondrocytes as the starting point, in order to further explore the mechanism of chondrocyte autophagy in osteoarthritis. The development process of osteoarthritis was studied from the perspective of chondrocytes, and the change of autophagy level had a significant impact on osteoarthritis. Chondrocyte autophagy is mainly determined by intracellular mitochondrial autophagy, so we are committed to finding relevant molecules. Through PI3K/AKT- and MAPK-related pathways, the biomarkers of chondrocyte autophagy were identified, and chondrocyte senescence, autophagy, and apoptosis based on osteoarthritis provided a constructive idea for the development of prospective targeted drugs and new therapies to slow down or prevent the progression of osteoarthritis.

Abstract Image

对骨关节炎中软骨细胞自噬机制和治疗策略的新认识。
骨关节炎(OA)是一种原因不明的慢性关节疾病,以继发性骨质增生和关节软骨退行性改变为特征。预计到 2050 年,将有超过 2.5 亿人受到这种疾病的影响,给整个世界带来巨大的社会经济压力。目前,还没有任何有效的药物可以治疗 OA 病症。随着时间的推移,软骨细胞会因老化或滥用药物而逐渐发生新陈代谢、结构和功能变化。软骨细胞平衡失调对骨关节炎的退行性进展有很大影响。通过不断回收和重建大分子或细胞器,自噬在个体的生长和发育过程中发挥着维持平衡的重要调节系统的作用。本综述以软骨细胞为切入点,建立了自噬与骨关节炎之间的紧密联系,以深入研究骨关节炎中软骨细胞自噬背后的机制。将确定软骨细胞自噬的生物标志物,并根据 OA 中软骨细胞的衰老、自噬和凋亡,开发出减缓或预防 OA 病程的前瞻性靶向药物和新型治疗方法。关键信息:目前,还没有任何药物能有效治疗 OA。我们希望通过探索骨关节炎病程中的特定靶点,促进治疗策略的进步。骨关节炎的退行性进展在很大程度上受到软骨细胞平衡失调的影响。通过大分子或细胞器的不断恢复和重建,自噬是个体生长发育过程中维持体内平衡的重要调节系统。本文以软骨细胞为切入点,建立自噬与骨关节炎的密切关系,以进一步探讨软骨细胞自噬在骨关节炎中的作用机制。从软骨细胞的角度研究了骨关节炎的发展过程,发现自噬水平的变化对骨关节炎有重要影响。软骨细胞自噬主要由细胞内线粒体自噬决定,因此我们致力于寻找相关分子。通过PI3K/AKT和MAPK相关通路,确定了软骨细胞自噬的生物标志物,基于骨关节炎的软骨细胞衰老、自噬和凋亡为开发前瞻性靶向药物和新疗法提供了建设性思路,以延缓或预防骨关节炎的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Molecular Medicine-Jmm
Journal of Molecular Medicine-Jmm 医学-医学:研究与实验
CiteScore
9.30
自引率
0.00%
发文量
100
审稿时长
1.3 months
期刊介绍: The Journal of Molecular Medicine publishes original research articles and review articles that range from basic findings in mechanisms of disease pathogenesis to therapy. The focus includes all human diseases, including but not limited to: Aging, angiogenesis, autoimmune diseases as well as other inflammatory diseases, cancer, cardiovascular diseases, development and differentiation, endocrinology, gastrointestinal diseases and hepatology, genetics and epigenetics, hematology, hypoxia research, immunology, infectious diseases, metabolic disorders, neuroscience of diseases, -omics based disease research, regenerative medicine, and stem cell research. Studies solely based on cell lines will not be considered. Studies that are based on model organisms will be considered as long as they are directly relevant to human disease.
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